[Show abstract][Hide abstract] ABSTRACT: Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC).
The Korean Journal of Pathology 08/2014; 48(4):263-9. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma.
[Show abstract][Hide abstract] ABSTRACT: Although, gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to that of Western countries. However, there is no Korean multidisciplinary guideline for gastric cancer and thus, a guideline adequate for domestic circumstances is required. Experts from related societies developed 22 recommendation statements for the diagnosis (n=9) and treatment (n=13) based on relevant key questions. Evidence levels based on systematic review of literatures were classified as five levels from A to E, and recommendation grades were classified as either strong or weak. The topics of this guideline cover diagnostic modalities (endoscopy, endoscopic ultrasound, radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, radiotherapy) and pathologic evaluation. External review of the guideline was conducted at the finalization phase. (Korean J Gastroenterol 2014;63:66-81).
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 02/2014; 63(2):66-81.
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B virus (HBV) replication detected before the resection of hepatocellular carcinoma (HCC) is to be controlled by antiviral agents. However, management strategy for patients with preoperatively undetectable HBV DNA without antiviral therapy is not clearly delineated. This study investigated viral reactivation after the liver resection in non-replicating HBV DNA related HCC patients and its impact on the surgical outcome.
From 198 patients that underwent liver resection due to HBV related HCC, 101 patients who had serially checked serum HBV DNA were analyzed.
From 101 patients, 33 patients had baseline undetectable HBV DNA. Eleven patients (11/33, 33.3%) had viral replication after the liver resection. The postoperative viral reactivation (HR: 2.144; 95% CI: 1.122-4.097; p=0.021), along with existence of satellite nodules (HR: 3.034; 95% CI: 1.1.376-6.689; p=0.006), existence of microvascular invasion (HR: 2.479; 95% CI: 1.303-4.718; p=0.006), and HBeAg positivity (HR: 2.059; 95% CI: 1.155-3.670; p=0.014) predicted recurrence after the surgery. Quantification of intrahepatic total and covalently closed circular DNA (cccDNA) was done in 14 patients whose baseline serum HBV DNA was undetectable without the use of antiviral agent. Amount of intrahepatic cccDNA expressed as copies/hepatocyte in patients with postoperative viral reactivation showed significantly higher than those in patients with sustained negative serum HBV DNA (p=0.010).
This study shows that naturally suppressed preoperative HBV without application of antiviral agent does not ensure undetectable serum HBV after the surgery, and postoperative viral reactivation might be associated with HCC recurrence.
Journal of Gastroenterology and Hepatology 12/2013; · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Self-made tissue punches can be effectively used to punch holes in blank recipient paraffin blocks and extract tissue cores from the donor paraffin blocks for the low-cost construction of tissue microarrays (TMAs). However, variable degrees of section distortion and loss of the tissue cores can occurs during cutting of the TMAs, posing technical problems for in-house manual construction of high-density TMAs. We aimed to update the method for in-house manual TMA construction to improve the quality of high-density TMAs.
Blocks of agarose gel were subjected to the standard tissue processing and embedding procedure to prepare recipient agarose-paraffin blocks. The self-made tissue punches and recipient agarose-paraffin blocks were used to construct TMAs, which were completely melted and re-embedded in paraffin to make finished TMA blocks.
The donor tissue cores were completely integrated into the surrounding paraffin of the recipient blocks. This method enabled us to construct high-density TMAs with significantly less section distortion or loss of tissue cores during microtomy.
Simple and inexpensive construction of high-density and high-quality TMAs can be warranted by using paraffinized agarose gels as recipient blocks.
The Korean Journal of Pathology 06/2013; 47(3):238-44. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients.
We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report.
Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms.
A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.
The Korean Journal of Pathology 06/2013; 47(3):227-37. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of early colorectal epithelial neoplasm (ECEN) is increasing, and its pathologic diagnosis is important for patient care. We investigated the incidence of ECEN and the current status of its pathologic diagnosis.
We collected datasheets from 25 institutes in Korea for the incidence of colorectal adenoma with high grade dysplasia (HGD) and low grade dysplasia in years 2005, 2007, and 2009; and early colorectal carcinoma in the year 2009. We also surveyed the diagnostic terminology of ECEN currently used by the participating pathologists.
The average percentage of diagnoses of adenoma HGD was 7.0%, 5.0%, and 3.4% in years 2005, 2007, and 2009, respectively. The range of incidence rates of adenoma HGD across the participating institutes has gradually narrowed over the years 2005 to 2009. The incidence rate of early colorectal carcinoma in the year 2009 was 21.2%. The participants did not share a single criterion or terminology for the diagnosis of adenoma HGD. The majority accepted the diagnostic terms that distinguished noninvasive, mucosal confined, and submucosal invasive carcinoma.
Further research requirements suggested are a diagnostic consensus for the histopathologic diagnosis of ECEN; and standardization of diagnostic terminology critical for determining the disease code.
The Korean Journal of Pathology 06/2013; 47(3):245-51. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small intestinal adenocarcinomas (SIACs) are rare, and their molecular pathogenesis is largely unknown. To define the roles of E-cadherin and β-catenin, we performed immunohistochemistry for E-cadherin and β-catenin in 194 surgically resected SIACs with tissue microarrays and compared the data with clinicopathologic factors, including survival rates of patients with SIAC. Loss of E-cadherin expression and aberrant β-catenin expression were observed in 41.8% (81/194 cases) and 40.7% (79/194 cases) of SIACs, respectively. Combined loss of E-cadherin and aberrant β-catenin expression was observed in 24.2% (47/194 cases) of SIACs, and this feature was most frequently observed in mucinous adenocarcinomas and signet ring cell carcinomas (P < .001), poorly differentiated and undifferentiated carcinomas (P < .001), and tumors with advanced pT classification (P = .03). Survival times for patients with SIAC with both loss of E-cadherin and aberrant β-catenin expression (median, 13.9 months) were significantly shorter than those for patients without aberrant expression of both proteins (49.9 months), as determined by univariate (P < .001) and multivariate (P = .01) analyses. In conclusion, loss of E-cadherin and aberrant β-catenin expression correlate with poorly differentiated tumors, advanced T classification, and decreased patient survival time; therefore, it could be a prognostic factor in patients with SIAC.
American Journal of Clinical Pathology 02/2013; 139(2):167-76. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case of peripheral primitive neuroectodermal tumor of the small bowel mesentery with osseous component is reported. A 23-year-old man was admitted to our hospital because of acute severe abdominal pain. Abdominal computed tomography revealed a large solid and cystic, oval shaped mass, measuring 11.0×6.0 cm in the pelvic cavity. Histologically the resected lesion consisted of sheets of undifferentiated small round cells forming Homer-Wright rosettes and perivascular pseudorosettes, and showed areas of osteoid and bone formation. Immunohistochemical studies revealed that tumor cells expressed positivity against CD99 (MIC2), CD57, neuron-specific enolase, and vimentin. Fluorescence in situ hybridization study revealed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement on chromosome 22q12. To the authors' knowledge this is the first documentation of a peripheral neuroectodermal tumor with osteoid and bone formation of the small bowel mesentery.
The Korean Journal of Pathology 02/2013; 47(1):77-81. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: A metabolomic study of biomarkers associated with dimethylnitrosamine (DMN)-induced hepatic fibrosis in Sprague-Dawley rats was performed using GC-MS. The clinical chemistry of the collected blood and the histopathology of excised liver samples were examined, and urine samples were prepared by solvent extraction. Results: Through pattern analysis, the DMN-treated group was divided into two subgroups based on the aspartate aminotransferase (AST) levels compared with the control, a moderately higher group (DMN subgroup A) and a significantly higher group (DMN subgroup B). Uric acid, orotic acid, N-phenylacetylglycine and glutaric acid were biomarkers for DMN subgroup A, aminomalonic acid was a biomarker for DMN subgroup B, and arabitol level distinguished control versus DMN treatment regardless of AST level. Conclusion: This study suggests that the identification and profiling of AST level-related metabolites may be useful as a diagnostic tool and for the study of the mechanism of liver fibrosis induced by DMN.
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic Heller myotomy with antireflux procedure is considered to be a standard treatment for achalasia. Recently, peroral endoscopic myotomy (POEM) was developed and performed on patients with achalasia. However, there is no report on POEM use in South Korea. The aim of this study was to evaluate the technical feasibility of POEM in a porcine model.
POEM was performed on two mini pigs. We performed upper endoscopy under general anesthesia. A submucosal tunnel was created and the circular muscle layer was incised using several knives. The mucosal entry was closed using resolution clips. We performed a follow-up endoscopy and sacrificed the pigs 2 weeks after the POEM. The myotomy site was evaluated grossly and histologically.
POEM was successfully performed on the two mini pigs. No injuries to any abdominal or mediastinal structures occurred. Two weeks after the POEM, the esophageal mucosa healed without any endoscopic evidence of complications. Necropsy revealed that the circular muscle layer was completely lost and replaced with fibrotic tissue.
We found that POEM is a technically feasible method which can be performed on an animal model. However, to ensure safe use on patients with achalasia, further studies on technical methods and long-term follow-up examinations are required.
[Show abstract][Hide abstract] ABSTRACT: Dietary restriction (DR) has many beneficial effects, but the detailed metabolic mechanism remains largely unresolved. As diet is essentially related to metabolism, we investigated the metabolite profiles of urines from control and DR animals using NMR and LC-Mass metabolomic approaches. Multivariate analysis presented distinctive metabolic profiles and marker signals from glucuronide and glycine conjugations pathways in the DR group. Broad profiling of the urine phase II metabolites with neutral loss scanning showed that glucuronide and glycine conjugation metabolites are generally higher in the DR group. The up-regulation of the phase II detoxifications in the DR group were confirmed by mRNA and protein expression levels of the UGT's and GLYAT's in actual liver tissues. Histopathology and serum biochemistry showed that the DR had beneficial effects of low serum ALT level and low glycogen granules in liver. In addition, the Nrf-2 signaling pathway was shown to be up-regulated, providing a mechanistic clue for the enhanced phase II detoxification in liver tissue. Taken together, our metabolomic and biochemical studies provide a possible metabolic perspective in understanding the complex mechanism of the beneficial effects of DR.
[Show abstract][Hide abstract] ABSTRACT: Advances of tissue microarray (TMA) technology have enabled simultaneous in situ analysis of biomarker expression in a large number of archived pathology specimens. However, the relatively high cost of TMA construction may hamper many researchers from using this essential tool of modern pathology research. We discuss methods for making TMA kits and recipient blocks for manual construction of high-density TMAs at low cost.
Ordinary cannula piercing needles, hypodermic needles, bone marrow biopsy needles, metallic ink cartridges of ballpoint pens, and disposable skin biopsy punches were used to construct self-made manual TMA kits. The recipient blocks were manufactured by boring holes in the conventional bare paraffin blocks. A mini electric hand drill and a microcompound table assembled on a drill stand were used to maximize the capacity of the recipient blocks.
By using TMA kits made from cannula piercing needles (16- and 18-gauge), it was possible to construct TMAs with 1 mm×140 cores, 0.6 mm×320 cores, 2 mm×70 cores, 3 mm×35 cores, and 5 mm×12 cores. The capacity of the recipient blocks could be dramatically increased by drilling holes.
Construction of TMAs using self-made TMA kits is an inexpensive alternative to construction of TMAs using commercial devices.
The Korean Journal of Pathology 12/2012; 46(6):562-8. · 0.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Small intestinal adenocarcinomas (SACs) are rare malignancies of the alimentary tract with uncertain carcinogenesis. METHODS: We investigated the expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically resected SACs, using tissue microarray technology. RESULTS: Twenty-four of the 188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0; 12.8%). Eighty-four and 31 cases were moderately and strongly positive, respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed that the expression of Smad4/DPC4 was related to an increased risk of lymphatic invasion but not to other clinicopathological features of the tumors (tumor location, differentiation, growth pattern, T stage, direct invasion, vascular invasion, and nodal metastasis). There was no significant association between Smad4/DPC4 expression and patient survival. CONCLUSIONS: The present research is the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with clinicopathologic correlation. Future studies should focus on the immunohistochemical and molecular characteristics of SACs to clarify their tumorigenesis.
Korean journal of pathology. 10/2012; 46(5):415-422.
[Show abstract][Hide abstract] ABSTRACT: Cancer registries play a fundamental role in cancer control and multicenter collaborative research. Recently, the need for reassessment of cancer registry criteria has arisen due to the newly released 2010 World Health Organization (WHO) classification. Accordingly, development of new coding guidelines for cancer is necessary to improve the quality of cancer registries, as well as to prevent conflicts that may arise when seeking medical insurance compensation.
With funding from the Management Center for Health Promotion, 35 members of the Gastrointestinal Pathology Study Group and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated in a second workshop for gastrointestinal tumor registration in Korea.
The topics of gastric epithelial tumor, colonic intramucosal carcinoma, neuroendocrine tumor (NET), gastrointestinal stromal tumor (GIST) and appendiceal mucinous tumor were discussed for new coding guidelines. A survey was then conducted among 208 members of the KSP for a consensus of the guidelines proposed in the workshop.
Although a few issues were set aside for further discussion, such as coding for non-gastric GIST and some types of NET, the members agreed upon most of the proposed guidelines. Therefore, we suggest using the newly revised International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) coding guidelines for registering gastrointestinal tumors in Korea.
Korean journal of pathology. 10/2012; 46(5):443-53.
[Show abstract][Hide abstract] ABSTRACT: Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the ≤ 40 yr-old group and 261 cases of > 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.
Journal of Korean medical science 09/2012; 27(9):1027-36. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.
Cancer Research and Treatment 09/2012; 44(3):157-65. · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report here a rare case of granular cell astrocytoma. A 75-year-old man was admitted to Inha University Hospital with a three-month history of language deterioration. In a magnetic resonance imaging, a 6.5 cm-sized heterogeneous enhancing mass was seen in both the frontal lobes and the anterior genu of the corpus callosum. A stereotactic biopsy was performed. The tumor was composed of large and small round cells with abundant intracytoplasmic granules. The nuclei were bland, round to oval, and often eccentrically located. The cytoplasm of the tumor cells was positive for glial fibrillary acidic protein and S-100 protein.
Korean journal of pathology. 08/2012; 46(4):370-2.
[Show abstract][Hide abstract] ABSTRACT: We report a case of gastritis cystica porfunda (GCP) associated with gastric carcinoma with lymphoid stroma (CLS). There was dysplastic change in the transitional area between GCP and CLS. Epstein-Barr virus (EBV) in situ hybridization (ISH) revealed positive reaction at the dysplastic area as well as at the CLS area. Immunohistochemical staining disclosed that dysplastic epithelium was similar to GCP in CK 20, MUC5AC, and E-cadherin expression, but similar to CLS in MUC6, CEA, p53, c-erb-B2, and EBV-ISH expression. Results of the EBV-ISH suggested that EBV infection may play a role in dysplastic change.
Pathology International 05/2012; 62(5):351-5. · 1.72 Impact Factor